Standard therapies for brain tumors include maximal surgical resection, radiation therapy, and chemotherapy. However, even with these interventions, these tumors are universally fatal, often within months. MRI with gadolinium (Gd)-based contrast agents is the current clinical standard for evaluating brain tumors. However, Gd enhancement, although it depicts the disruption of the blood brain barrier (BBB), is not specific for tumor proliferation. Gd-enhanced MRI is limited in that (i) many low-grade and even some high-grade gliomas (10% of glioblastoma multiforme and 20-30% of anaplastic astrocytoma) demonstrate no Gd-enhancement, and (ii) separating recurrent tumor from other causes of BBB dysfunction, such as treatment-induced necrosis, is extremely difficult. In addition, there has recently been increasing concern about the long-term safety of Gd exposure. Diffusion NMR can provide information noninvasively about tissue microstructure and microdynamics at a scale comparable to cell dimensions. The goal of this proposal is to demonstrate that these unique diffusion patterns and tumor microstructures at the near-cellular level can distinguish between recurrent tumors and radiation effects using the rat glioma and radiation necrosis models. The specific aims are: (1) To define the water diffusion patterns associated with rat glioma models in vivo, using high-resolution DTI at 4.7T. (2) To define water diffusion patterns associated with histologically confirmed radiation-induced necrosis after focal radiation to the caudate-putamen in healthy rats. (3) To assess the ability of high-resolution DTI at 4.7T to distinguish between proliferating tumor and radiation-induced injury in vivo. Differentiation of tumor recurrence from radiation injury remains a diagnostic dilemma in the management of human brain tumors. If our goal is achieved, the unique capability of high-resolution DTI could significantly enhance the diagnostic accuracy of MRI for brain cancer noninvasively. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to demonstrate the possibility that unique diffusion patterns and related tumor microstructures at the near-cellular level can distinguish between recurrent tumors and radiation effects using the rat glioma and radiation necrosis models. If our goal is achieved, the unique capability of high-resolution diffusion tensor MRI could significantly enhance the diagnostic accuracy of MRI for brain cancer noninvasively.